Although the visual cortex receives information at multiple temporal patterns, much of the research in the field has focused only on intervals shorter than 1 second. Consequently, there is almost no ...information on what happens at longer temporal intervals. We have tried to address this question recording neuronal populations of the primary visual cortex during visual stimulation with repetitive grating stimuli and intervals ranging from 1 to 7 seconds. Our results showed that firing rate and response stability were dependent of interval duration. In addition, there were collective oscillations with different properties in response to changes in intervals duration. These results suggest that visual cortex could encode visual information at several time scales using oscillations at multiple frequencies.
The presence of stromal tumor-infiltrating lymphocytes (TILs) is associated with increased pathologic complete response (pCR) and improved outcomes in HER2-positive early-breast cancer (BC) treated ...with anti-HER2-based chemotherapy. In the absence of chemotherapy, the association of TILs with pCR following anti-HER2 therapy-only is largely unknown.
The PAMELA neoadjuvant trial treated 151 women with HER2-positive BC with lapatinib and trastuzumab and hormonal therapy if hormone receptor (HR)-positive for 18 weeks. Percentage of TILs and tumor cellularity were determined at baseline (N = 148) and at day 15 (D15) of treatment (N = 134). Associations of TILs and tumor cellularity with pCR in the breast were evaluated. A combined score based on tumor cellularity and TILs (CelTIL) measured at D15 was derived in PAMELA, and validated in D15 samples from 65 patients with HER2-positive disease recruited in the LPT109096 neoadjuvant trial, where anti-HER2 therapy-only was administer for 2 weeks, then standard chemotherapy was added for 24 weeks.
In PAMELA, baseline and D15 TILs were significantly associated with pCR in univariate analysis. In multivariable analysis, D15 TILs, but not baseline TILs, were significantly associated with pCR. At D15, TILs and tumor cellularity were found independently associated with pCR. A combined score (CelTIL) taking into account both variables was derived. CelTIL at D15 as a continuous variable was significantly associated with pCR, and patients with CelTIL-low and CelTIL-high scores had a pCR rate of 0% and 33%, respectively. In LPT109096, CelTIL at D15 was found associated with pCR both as a continuous variable and as group categories using a pre-defined cut-off (75.0% versus 33.3%).
On-treatment TILs, but not baseline TILs, are independently associated with response following anti-HER2 therapy-only. A combined score of TILs and tumor cellularity measured at D15 provides independent predictive information upon completion of neoadjuvant anti-HER2-based therapy.
NCT01973660.
Summary
This paper presents a control technique for output tracking of reference signals in continuous‐time dynamical systems. The technique is comprised of the following three elements: (i) a ...fluid‐flow version of the Newton–Raphson method for solving algebraic equations, (ii) a system‐output prediction which has to track the future reference signal, and (iii) a speedup of the control action for enhancing the tracker's accuracy and, in some cases, stabilizing the closed‐loop system. The technique can be suitable for linear and nonlinear systems, implementable by simple algorithms, and can track reference points as well as time‐dependent reference signals. Though inherently local, the tracking controller is proven to have a global convergence for a class of linear systems. The derived theoretical results of the paper include convergence of the tracking controller and error analysis, and are supported by illustrative simulation and laboratory experiments.
Since Darwin's time, the role of crop wild relatives (CWR), landraces, and cultivated genepools in shaping plant diversity and boosting food resources has been a major question ....
Single nucleotide polymorphism (SNP) markers have become a genetic technology of choice because of their automation and high precision of allele calls. In this study, our goal was to develop 94 SNPs ...and test them across well-chosen common bean (Phaseolus vulgaris L.) germplasm. We validated and accessed SNP diversity at 84 gene-based and 10 non-genic loci using KASPar technology in a panel of 70 genotypes that have been used as parents of mapping populations and have been previously evaluated for SSRs. SNPs exhibited high levels of genetic diversity, an excess of middle frequency polymorphism, and a within-genepool mismatch distribution as expected for populations affected by sudden demographic expansions after domestication bottlenecks. This set of markers was useful for distinguishing Andean and Mesoamerican genotypes but less useful for distinguishing within each gene pool. In summary, slightly greater polymorphism and race structure was found within the Andean gene pool than within the Mesoamerican gene pool but polymorphism rate between genotypes was consistent with genepool and race identity. Our survey results represent a baseline for the choice of SNP markers for future applications because gene-associated SNPs could themselves be causative SNPs for traits. Finally, we discuss that the ideal genetic marker combination with which to carry out diversity, mapping and association studies in common bean should consider a mix of both SNP and SSR markers.
Research needs in breast cancer Cardoso, F.; Harbeck, N.; Barrios, C.H. ...
Annals of oncology,
02/2017, Volume:
28, Issue:
2
Journal Article
Peer reviewed
Open access
New research questions emerge as medical needs continue to evolve and as we improve our understanding of cancer biology and treatment of malignancies. Although significant advances have been made in ...some areas of breast cancer research resulting in improvements in therapies and outcomes over the last few decades, other areas have not benefited to the same degree and we continue to have many gaps in our knowledge. This article summarizes the 12 short and medium-term clinical research needs in breast cancer deemed as priorities in 2016 by a panel of experts, in an attempt to focus and accelerate future research in the most needed areas: (i) de-escalate breast cancer therapies in early breast cancer without sacrificing outcomes; (ii) explore optimal adjuvant treatment durations; (iii) develop better tools and strategies to identify patients with genetic predisposition; (iv) improve care in young patients with breast cancer; (v) develop tools to speed up drug development in biomarker-defined populations; (vi) identify and validate targets that mediate resistance to chemotherapy, endocrine therapy and anti-HER2 therapies; (vii) evaluate the efficacy of local-regional treatments for metastatic disease; (viii) better define the optimal sequence of treatments in the metastatic setting; (ix) evaluate the clinical impact of intra-patient heterogeneity (intra-tumor, inter-tumor and inter-lesion heterogeneity); (x) better understand the biology and identify new targets in triple-negative breast cancer; (xi) better understand immune surveillance in breast cancer and further develop immunotherapies; and (xii) increase survivorship research efforts including supportive care and quality of life.
Introduction
Chronic insomnia, resistant to different treatments (pharmacological, sleep hygiene and cognitive-behavioral therapy) remains one of the greatest challenges in our daily practice as ...psychiatrists. The pharmacological options include benzodiazepines and their analogues (zolpidem, zopiclone, etc.). However, when trying to treat chronic insomnia the use of off-label drugs, including antidepressants with sedative action (such as trazodone), antipsychotics or antiepiletic drugs, is not uncommon.
Perampanel is a non-competitive AMPA receptor antagonist, marketed for the treatment of partial onset epilepsy and primary generalized tonic-clonic seizures. It has been used in the treatment of chronic insomnia with positive results and it has shown to improve the quality of sleep in a recent observational retrospective cohort study.
The most frequent adverse effects of Perampanel include dizziness and drowsiness. Perampanel can also cause psychiatric and behavioral adverse effects, aggression and irritability in up to 10% of patients, as well as depression, and suicidal ideation, with higher rates in patients with psychiatric history.
Objectives
To draw attention to possible adverse effects of Perampanel and to add knowledge to improve the treatment for chronic insomnia.
Methods
Case report and non-systematic literature review of the current data.
Results
A 33 year old woman with Anorexia Nervosa was admitted to the psychiatric hospitalization unit due to suicidal ideation and a history of chronic insomnia. Perampanel was started at a dose of 2mg/day, progressively titrated to 6mg/day, following patient’s informed consent. A week after the initiation of treatment, her sleep pattern had improved but she became aggressive, showed low tolerability to minor frustrations and suffered from an intensification of suicidal ideation. She became extremely hostile to the personnel, had severe tantrums and deliberate self injurious behavior. Perampanel was discontinued and in less than a week her aggressive behavior succumbed. Although she was not re-exposed to Perampanel the symptoms she presented are considered a very likely adverse drug reaction. Levomepromazine 20mg/day and Lormetazepam 0.5mg/day were reinstated as a treatment for insomnia.
Conclusions
Psychiatric comorbidity is known to be a risk factor for behavioral adverse effects of Perampanel. Therefore Perampanel as a treatment for chronic insomnia needs a careful individual benefit-risk assessment and monitoring for adverse effects.
Disclosure of Interest
None Declared
Grafting typically offers a shortcut to breed tree orchards throughout a multidimensional space of traits. Despite an overwhelming spectrum of rootstock-mediated effects on scion traits observed ...across several species, the exact nature and mechanisms underlying the rootstock-mediated effects on scion traits in cacao (
L.) plants often remain overlooked. Therefore, we aimed to explicitly quantify rootstock-mediated genetic contributions in recombinant juvenile cacao plants across target traits, specifically cadmium (Cd) uptake, and its correlation with growth and physiological traits. Content of chloroplast pigments, fluorescence of chlorophyll
, leaf gas exchange, nutrient uptake, and plant biomass were examined across ungrafted saplings and target rootstock × scion combinations in soils with contrasting levels of Cd. This panel considered a total of 320 progenies from open-pollinated half-sib families and reciprocal full-sib progenies (derived from controlled crosses between the reference genotypes IMC67 and PA121). Both family types were used as rootstocks in grafts with two commercial clones (ICS95 and CCN51) commonly grown in Colombia. A pedigree-based best linear unbiased prediction (
-BLUP) mixed model was implemented to quantify rootstock-mediated narrow-sense heritability (
) for target traits. A Cd effect measured on rootstocks before grafting was observed in plant biomass, nutrient uptake, and content of chloroplast pigments. After grafting, damage to the Photosystem II (PSII) was also evident in some rootstock × scion combinations. Differences in the specific combining ability for Cd uptake were mostly detected in ungrafted rootstocks, or 2 months after grafting with the clonal CCN51 scion. Moderate rootstock effects (
> 0.1) were detected before grafting for five growth traits, four nutrient uptake properties, and chlorophylls and carotenoids content (
= 0.19, 95% CI 0.05-0.61,
= 0.7). Such rootstock effects faded (
< 0.1) when rootstock genotypes were examined in soils without Cd, or 4 months after grafting. These results suggest a pervasive genetic conflict between the rootstock and the scion genotypes, involving the triple rootstock × scion × soil interaction when it refers to Cd and nutrient uptake, early growth, and photosynthetic process in juvenile cacao plants. Overall, deepening on these findings will harness early breeding schemes of cacao rootstock genotypes compatible with commercial clonal scions and adapted to soils enriched with toxic levels of Cd.
•Random non-autonomous logistic-type differential equations are studied.•Random Variable Transformation method and Karhunen–Love expansion are combined.•First probability density function of the ...solution stochastic process is determined.•Numerical simulations for the mean, variance and PDF of the solution are performed.•A wide range of PDFs for input data are considered in numerical experiments.
This paper deals with the study, from a probabilistic point of view, of logistic-type differential equations with uncertainties. We assume that the initial condition is a random variable and the diffusion coefficient is a stochastic process. The main objective is to obtain the first probability density function, f1(p, t), of the solution stochastic process, P(t, ω). To achieve this goal, first the diffusion coefficient is represented via a truncation of order N of the Karhunen–Loève expansion, and second, the Random Variable Transformation technique is applied. In this manner, approximations, say f1N(p,t), of f1(p, t) are constructed. Afterwards, we rigorously prove that f1N(p,t)⟶f1(p,t) as N → ∞ under mild conditions assumed on input data (initial condition and diffusion coefficient). Finally, three illustrative examples are shown.
How does the news media respond to health emergencies abroad? Between 2015 and 2018, Zika virus spread rapidly throughout Latin America before arriving in the continental United States. Despite the ...risks to adults and newborns, it is unclear how media coverage developed and framed the threat for its audience. In this paper, we argue that while the frequency of coverage was responsive to infections, its content failed to promote proactive health behaviour. To assess these claims, we analyse each of 442 articles dealing with Zika virus published by The New York Times from 2015–18. We find that the amount of coverage reflected infections but did not change once the disease emerged in the US. Furthermore, content analysis using Linguistic Inquiry and Word Count software reveals that coverage emphasised differences between communities (those affected and those at home) and that present and past time orientations dominated coverage as opposed to future time orientations.
نبذة مختصرة
كيف تستجيب وسائل الإعلام لحالات الطوارئ الصحية في الخارج ؟ من عام 2015 إلى عام 2018، انتشر مرض فيروس زيكا بسرعة في جميع أنحاء أمريكا اللاتينية قبل وصوله إلى الولايات المتحدة القارية. على الرغم من المخاطر التي يتعرض لها البالغون والأطفال حديثي الولادة، فمن غير الواضح كيف استجابت التغطية الإعلامية وصورت المخاطر لمتتبعيها. في هذا المقال، نناقش بأنه على الرغم من أن تكرار التغطية كان مستجيباً لانتشار العدوى إلا أن محتواها فشل في تعزيز السلوك الصحي الاستباقي. لتقييم هذه الادعاءات، سنقوم بتحليل كل مقال يتناول فيروس زيكا تم نشره بين 2015–2018 بواسطة صحيفة نيويورك تايمز. نجد أن مقدار التغطية ينعكس على مدى انتشار العدوى لكنها لم تتغير بمجرد وصول الفيروس إلى الولايات المتحدة. علاوة على ذلك، يكشف تحليل المحتوى باستخدام برنامج تحليل النصوص LIWC أن التغطية أكدت الاختلافات بين المجتمعات (المتأثرة وتلك الموجودة في المنزل) وأن التوجهات الزمنية الحالية والماضية سيطرت على التغطية بدلاً من التوجهات الزمنية المستقبلية.
الكلمات المفتاحية: الوباء، التأطير، التغطية الإعلامية، الصحة العامة، فيروس زيكا
摘要
新闻媒体如何应对国外的卫生突发事件？从2015年到2018年，寨卡病毒疾病在抵达美国大陆之前迅速蔓延整个拉丁美洲。尽管成人和新生儿面临风险，但目前还不清楚媒体报道是如何为其受众回应和定调风险的。在这篇文章中，我们认为，虽然报道的频率对感染有响应，但其内容未能促进主动的健康行为。为了评估这些主张，我们分析了《纽约时报》在2015–2018年间发表的每一篇涉及寨卡病毒的文章（442篇）。我们发现，报道数量反映了感染情况，但在病毒到达美国后，报道数量并没有改变。此外，使用LIWC文本分析程序进行的内容分析显示，报道强调了群体之间的差异（受影响的人和居家的人），而且现在和过去的时间取向在报道中占主导地位，未来的时间取向并没有占主导。
关键词: 流行病，定调，媒体报道，公共卫生，寨卡病毒
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